The present invention disclosed herein relates to a monoclonal antibody which specifically recognizing B cell lymphoma cell and a use thereof. More specifically, the present invention relates to a monoclonal antibody; a pharmaceutical composition for preventing or treating B cell lymphoma, including the monoclonal antibody; a composition for diagnosing B cell lymphoma including the monoclonal antibody; a method for providing information for diagnosing B cell lymphoma using the monoclonal antibody; a chimeric antigen receptor (CAR) protein including i) the antibody, ii) a transmembrane domain, and iii) an intracellular signaling domain; a recombinant vector which expresses the CAR protein; a CAR-modified T cell transformed with the recombinant vector; a pharmaceutical composition for preventing or treating B cell lymphoma including the CAR-modified T cell; and an antibody-drug conjugate in which the monoclonal antibody and a drug are conjugated.
B cell lymphoma consists of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). NHL is blood cancer which most frequently occurs in adults. NHL occurred in more than 66,000 people in the U.S. in 2008 and the annual occurrence rate is increased by 4%. Additionally, the occurrence of lymphoma is steadily increasing while those of some other cancers are decreasing.
Most of lymphoma/leukemia occurring from B cells expresses CD19 and CD20 on the cell surface, and therefore, based on this, a monoclonal antibody which recognizes CD20 has been developed as a therapeutic agent for treating B cell lymphoma/leukemia. Anti-CD20 monoclonal antibodies remove cancer through various mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and induction of apoptosis. The anti-CD20 monoclonal antibody (rituximab), which was approved by USFDA as a treatment for B cell NHL in 1977, has been used since then as a standard therapeutic method for treating diffused large B cell lymphoma (DLBCL) and other B cell lymphoma/leukemia in such a manner that it was administered in combination with cyclophosphamide plus doxorubicin, vincristine, prednisone (CHOP). However, malignant B cells and rituximab, regardless of their high reactivity, have a low effect of complete cure of less than 10%. This phenomenon is because some of B cell lymphoma/leukemia cells reduce CD20 expression thereby evading the action of rituximab. Additionally, there is a limitation that normal B cells also express CD20 and thus normal B cells are also removed by rituximab. In this regard, those cancer patients administered with rituximab are removed of humoral immunities and thus there is a high possibility of occurrence of side effects such as occurrence of type B hepatitis, increase of viral infections, and multifocal leukoencephalopathy. Accordingly, there has been a demand for the development of a next generation monoclonal antibody which selectively binds to B cell lymphoma/leukemia cells.
Under these circumstances, the present inventors have eagerly endeavored to develop a monoclonal antibody which selectively recognizes only malignant B cells, resultantly, have produced a pool of hybridomas which react with B cell lymphoma, and subsequently have succeeded to develop a hybridoma and antibodies produced therefrom, wherein the hybridoma has an anticancer activity and does not recognize cancer cells other than normal B cells and B cell lymphoma but selectively recognizes B cell lymphoma when subjected to a few steps of screening through flow cytometry analysis. Additionally, the present inventors confirmed that the above antibody has excellent anticancer activity both in vitro and in vivo against B cell lymphoma, and that the antibody exhibits excellent anticancer activity when the antibody is used as a therapeutic agent for chimeric antigen receptor (CAR)-T cells. Consequently, the present inventors confirmed that the antibody can be used in various forms of anticancer treatments such as an antibody-/anticancer-therapeutic agent containing the antibody as a major effect of ADCC mechanism, antibody therapeutic agent such as radioisotopes/anticancer agents/toxins, etc., which are in a form being bound to anticancer substances, and CAR-T cell treatment using scFv. Finally, the present inventors completed the present invention.